Oxygen diffusion in ellipsoidal tumour spheroids

Oxygen plays a central role in cellular metabolism, in both healthy and tumour tissue. The presence and concentration of molecular oxygen in tumours has a substantial effect on both radiotherapy response and tumour evolution, and as a result the oxygen micro-environment is an area of intense research interest. Multi-cellular tumour spheroids closely mimic real avascular tumours, and in particular they exhibit physiologically relevant heterogeneous oxygen distribution. This property has made them a vital part of in vitro experimentation. For ideal spheroids, their heterogeneous oxygen distributions can be predicted from theory, allowing determination of cellular oxygen consumption rate (OCR) and anoxic extent. However, experimental tumour spheroids often depart markedly from perfect sphericity. There has been little consideration of this reality. To date, the question of how far an ellipsoid can diverge from perfect sphericity before spherical assumptions break down remains unanswered. In this work, we derive equations governing oxygen distribution (and, more generally, nutrient and drug distribution) in both prolate and oblate tumour ellipsoids, and quantify the theoretical limits of the assumption that the spheroid is a perfect sphere. Results of this analysis yield new methods for quantifying OCR in ellipsoidal spheroids, and how this can be applied to markedly increase experimental throughput and quality.

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Oxygen diffusion in ellipsoidal tumour spheroids

10.1101/271890 ◽

2018 ◽

Author(s):

David Robert Grimes ◽

Frederick J. Currell

Keyword(s):

Oxygen Consumption ◽

Oxygen Diffusion ◽

Drug Distribution ◽

Substantial Effect ◽

Experimental Models ◽

Oxygen Distribution ◽

New Methods ◽

Tumour Spheroids ◽

Cellular Oxygen

AbstractOxygen plays a central role in cellular metabolism, in both healthy and tumour tissue. The presence and concentration of molecular oxygen in tumours has a substantial effect on both radiotherapy response and tumour evolution, and as a result the oxygen micro-environment is an area of intense research interest. Multicellular tumour spheroids closely mimic real avascular tumours, and in particular they exhibit physiologically relevant heterogeneous oxygen distribution. This property has made them a vital part of in vitro experimentation. For ideal spheroids, their heterogeneous oxygen distributions can be predicted from theory, allowing determination of cellular oxygen consumption rate (OCR) and anoxic extent. However, experimental tumour spheroids often depart markedly from perfect sphericity. There has been little consideration of this reality. To date, the question of how far an ellipsoid can diverge from perfect sphericity before spherical assumptions breakdown remains unanswered. In this work we derive equations governing oxygen distribution (and more generally, nutrient and drug distribution) in both prolate and oblate tumour ellipsoids, and quantify the theoretical limits of the assumption that the spheroid is a perfect sphere. Results of this analysis yield new methods for quantifying OCR in ellipsoidal spheroids, and how this can be applied to markedly increase experimental throughput and quality.Author summaryMulticellular tumour spheroids (MCTS) are an increasingly important tool in cancer research, exhibiting non-homogeneous oxygen distributions and central necrosis. These are more similar to in situ avascular tumours than conventional 2D biology, rendering them exceptionally useful experimental models. Analysis of spheroids can yield vital information about cellular oxygen consumption rates, and the heterogeneous oxygen contribution. However, such analysis pivots on the assumption of perfect sphericity, when in reality spheroids often depart from such an ideal. In this work, we construct a theoretical oxygen diffusion model for ellipsoidal tumour spheroids in both prolate and oblate geometries. With these models established, we quantify the limits of the spherical assumption, and illustrate the effect of this assumption breaking down. Methods of circumventing this breakdown are also presented, and the analysis here suggests new methods for expanding experimental throughput to also include ellipsoidal data.

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Selective LC determination of cabergoline in the bulk drug and in tablets: In vitro dissolution studies

Chromatographia ◽

10.1016/s0009-5893(07)82061-3 ◽

2007 ◽

Vol 65 (9-10) ◽

pp. 561-567

Author(s):

A ONAL ◽

O SAGIRLI ◽

D SENSOY

Keyword(s):

In Vitro Dissolution ◽

Dissolution Studies ◽

Bulk Drug

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In Vitro Validation of an Automated Method Based on Color Doppler Imaging for Determination of Flow Volume in the Presence of Nonflat Velocity Distributions

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)88255-1 ◽

1998 ◽

Vol 31 (2) ◽

pp. 518A ◽

Cited By ~ 1

Author(s):

K Dennig

Keyword(s):

Color Doppler ◽

Color Doppler Imaging ◽

Doppler Imaging ◽

Flow Volume ◽

Automated Method

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Determination of in vitro „anti-aging„-effects of Ganoderma pfeifferi

Planta Medica ◽

10.1055/s-0030-1264580 ◽

2010 ◽

Vol 76 (12) ◽

Cited By ~ 1

Author(s):

W Jülich ◽

J Pörksen ◽

H Welzel ◽

U Lindequist

Keyword(s):

Aging Effects

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In vitro determination of the skin anti-aging potential of eleven South African plants

Planta Medica ◽

10.1055/s-0033-1352005 ◽

2013 ◽

Vol 79 (13) ◽

Author(s):

GN Ndlovu ◽

G Fouche ◽

W Cordier ◽

V Steenkamp ◽

M Tselanyane

Keyword(s):

South African ◽

South African Plants ◽

African Plants

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A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

Nuklearmedizin ◽

10.1055/s-0038-1624353 ◽

1987 ◽

Vol 26 (01) ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

S. Selvaraj ◽

M. R. Suresh ◽

G. McLean ◽

D. Willans ◽

C. Turner ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Tumor Cell ◽

T Antigen ◽

Human Carcinomas ◽

Animal Tumor ◽

Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

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Storage of Human Blood Platelets

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647709 ◽

1974 ◽

Vol 32 (02/03) ◽

pp. 405-416 ◽

Cited By ~ 3

Author(s):

M. R Hardeman ◽

Carina J L. Heynens

Keyword(s):

Storage Temperature ◽

Platelet Rich Plasma ◽

Blood Platelets ◽

Storage Period ◽

Serotonin Uptake ◽

Hypotonic Shock ◽

Glycolytic Intermediates

SummaryStorage experiments were performed at 4°, 25° and 37° C with platelet-rich plasma under sterile conditions. In some experiments also the effect of storing platelets at 4° C in whole blood was investigated.Before, during and after three days of storage, the platelets were tested at 37° C for their serotonin uptake and response to hypotonic shock. In addition some glycolytic intermediates were determined.A fair correlation was noticed between the serotonin uptake and hypotonic shock experiments. Both parameters were best maintained at 25° C. Also platelet counting, performed after the storage period, indicated 25° C as the best storage temperature. Determination of glycolytic intermediates did not justify any conclusion regarding the optimal storage temperature. Of the various anticoagulants studied, ACD and heparin gave the best results as to the serotonin uptake and hypotonic shock response, either with fresh or stored platelets. The use of EDTA resulted in the lowest activity, especially after storage.The results of these storage experiments in vitro, correspond well with those in vivo reported in the literature.

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DETERMINATION OF BLOOD CORTICOIDS USING THE IN VITRO RESIN UPTAKE OF 3H-PREDNISOLONE

Acta Endocrinologica ◽

10.1530/acta.0.0570023 ◽

1968 ◽

Vol 57 (1) ◽

pp. 23-32 ◽

Cited By ~ 2

Author(s):

Hironori Nakajima ◽

Mitsunori Murala ◽

Masumitsu Nakata ◽

Takeshi Naruse ◽

Seiji Kubo

Keyword(s):

Thyroid Function Test ◽

Normal Subjects ◽

Adrenal Function ◽

Function Test ◽

Before And After ◽

Adrenal Response ◽

Suppression Test

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.

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